46 research outputs found
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Energy balance effects on microRNA expression in a mouse model of pancreatic cancer
No full texttextPancreatic cancer is the fourth leading cause of cancer death in the United States, with a five-year survival rate under 5%. Given the disease’s deadliness, increasing our understanding of the molecular nature of the pancreatic cancer is key to developing more effective preventive measures and treatments. Dietary energy restriction (DER) has been shown to have potent anticancer effects in pancreatic cancer, but the mechanism of action has yet to be completely elucidated. Here we investigate the potential of altered microRNA expression as a mechanism by which DER exerts its anticancer effect. Using the Exiqon microRNA Array, we identified several microRNAs of interest for further study. This includes microRNA (mir) 669c, a known regulator of glutathione-S transferases (linked to carcinogen metabolism and oxidative stress) that increases with age. To our knowledge, this is the first exploration of the effects of DER (which is known to suppress oxidative stress and other processes associated with aging and cancer) on microRNA expression. These findings may provide the initial steps towards identifying novel targets for pancreatic cancer prevention or treatment.Institute for Cellular and Molecular Biolog
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The effect of obesity on postmenopausal mammary tumor growth and differentiation is p53-dependent
No full texttextThe adult prevalence of obesity in the United States exceeds 30% and obesity is associated with increased cancer risk and poor prognosis, including postmenopausal breast cancer. p53 is a tumor suppressor gene that responds to diverse cellular stress including DNA damage, oxidative stress and hypoxia. p53 is mutated in most human cancers, including postmenopausal breast cancer, and is involved in the regulation of lipogenic enzymes. However, the links between p53 and obesity in postmenopausal breast cancer are poorly understood. Here we test the hypothesis that the effect of obesity on mammary tumor growth is impacted by p53 status. The aim of this study was to determine how p53-deficient mammary tumor cells (relative to p53 wild-type cells) respond to obesity-driven tumor growth. To test this hypothesis, we used ovariectomized (OVX) C57BL/6 mice randomized to a control diet (n=40) or a diet-induced obesity (DIO) regimen (n=40) for 10 weeks. At the time, DIO mice were approximately 40% heavier (p<0.001) and had 45% greater adiposity (p<0.001) than control mice. Mice were then injected (in the 4th mammary fat pad) with either p53-deficient (p53+/-) or p53 wild-type (p53+/+) MMTV-Wnt-1 mammary tumor cells. Mice were monitored for tumor growth, killed when moribund, and tumors were collected at study end point. We found an interaction between diet and p53 status, with p53+/+ Wnt-1 tumors grown in DIO mice developing the more aggressive morphology compared to p53+/+ Wnt tumors in control mice while the observation was not seen in p53+/- Wnt tumors. From histopathological analysis we also discovered that the DIO regimen promotes local invasion of mammary tumor cells and alters the morphology of MMTV-Wnt-1 p53+/+ mammary tumors. Specifically, p53+/+ Wnt tumors grown in DIO mice displayed disorganized ductal structures characteristic of p53+/- tumors grown in control mice, and DIO exacerbated this aberrant morphology in p53+/- Wnt tumors. Moreover, immunohistological analyses showed that DIO reduces p53 protein expression while elevating Ki-67 expression only in the p53+/+ Wnt mammary tumors. These results suggest that p53 and DIO have interactive effects on mammary tumor growth, as p53+/+ Wnt tumors growing in DIO mice resulted in higher tumor grade similar to p53+/- Wnt tumors.Nutritional Science
Calorie restriction and cancer prevention: a mechanistic perspective
No full textStephen D Hursting12*, Sarah M Dunlap1, Nikki A Ford1, Marcie J Hursting3 and Laura M Lashinger12
Author Affiliations
1 Department of Nutritional Sciences, The University of Texas at Austin, 1400 Barbara Jordan Blvd, DPRI 2.834, Austin, TX, 78723, USA
2 Department of Molecular Carcinogenesis, The University of Texas-MD Anderson Cancer Center, Smithville, TX, USA
3 Clinical Science Consulting, Austin, TX, USACalorie restriction (CR) is one of the most potent broadly acting dietary interventions for inducing weight loss and for inhibiting cancer in experimental models. Translation of the mechanistic lessons learned from research on CR to cancer prevention strategies in human beings is important given the high prevalence of excess energy intake, obesity, and metabolic syndrome in many parts of the world and the established links between obesity-associated metabolic perturbations and increased risk or progression of many types of cancer. This review synthesizes findings on the biological mechanisms underlying many of the anticancer effects of CR, with emphasis on the impact of CR on growth factor signaling pathways, inflammation, cellular and systemic energy homeostasis pathways, vascular perturbations, and the tumor microenvironment. These CR-responsive pathways and processes represent targets for translating CR research into effective cancer prevention strategies in human beings.Nutritional [email protected]
Leucine supplementation differentially enhances pancreatic cancer growth in lean and overweight mice
No full textKristyn A Liu1†, Laura M Lashinger1†, Audrey J Rasmussen1† and Stephen D Hursting12*
Author Affiliations
1 Department of Nutritional Sciences, University of Texas at Austin, Austin, TX 78723, USA
2 Department of Molecular Carcinogenesis, University of Texas M.D. Anderson Cancer Center, 1808 Park Road 1c, Smithville, TX 78957, USABackground: The risk of pancreatic cancer, the 4th deadliest cancer for both men and women in the United States, is increased by obesity. Calorie restriction (CR) is a well-known dietary regimen that prevents or reverses obesity and suppresses tumorigenesis in a variety of animal models, at least in part via inhibition of mammalian target of rapamycin (mTOR) signaling. Branched-chain amino acids (BCAA), especially leucine, activate mTOR and enhance growth and proliferation of myocytes and epithelial cells, which is why leucine is a popular supplement among athletes. Leucine is also increasingly being used as a treatment for pancreatic cancer cachexia, but the effects of leucine supplementation on pancreatic tumor growth have not been elucidated. Results: Supplementation with leucine increased pancreatic tumor growth in both lean (104 ± 17 mm3 versus 46 ± 13 mm3; P <0.05) and overweight (367 ± 45 mm3 versus 230 ± 39 mm3; P <0.01) mice, but tumor enhancement was associated with different biological outcomes depending on the diet. In the lean mice, leucine increased phosphorylation of mTOR and downstream effector S6 ribosomal protein, but in the overweight mice, leucine reduced glucose clearance and thus increased the amount of circulating glucose available to the tumor. Conclusion: These findings show that leucine supplementation enhances tumor growth in both lean and overweight mice through diet-dependent effects in a murine model of pancreatic cancer, suggesting caution against the clinical use of leucine supplementation for the purposes of skeletal muscle enhancement in cachectic patients.Nutritional Science
Mechanistic Targets and Phytochemical Strategies for Breakingthe Obesity-Cancer Link
No full textThe prevalence of obesity, an established risk and progression factor for many cancers, has increased dramatically in many countries over the past three decades. Worldwide, an estimated 600 million adults are currently obese. Thus, a better understanding of the mechanistic links between obesity and cancer is urgently needed to identify intervention targets and strategies to offset the procancer effects of obesity. This review synthesizes the evidence on key biological mechanisms underlying the obesity-cancer association, with particular emphasis on obesity-associated enhancements in growth factor signaling, inflammation, and perturbations in the tumor microenvironment. These interrelated pathways and processes that are aberrantly regulated in obese individuals represent mechanism-based targets for disrupting the obesity-cancer link using phytochemicals
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The Austin Garden Landscape Project
No full textThe Austin Garden Landscape Project
Amy Hoover, MS
The University of Texas at Austin, 2020
Supervisor: Jaimie Davis, PhD, RD, Associate Professor, Department of Nutritional Sciences
Co-Supervisor: Laura M. Lashinger, PhD, Assistant Professor of Instruction, Department of Nutritional Sciences
Background: Gardening programs have been utilized by schools for over thirty years to provide an outdoor hands-on science learning experience, teach nutrition knowledge and food safety practices, and promote environmental awareness. Numerous studies over the past two decades have shown that school gardening programs improve dietary intake, academic performance and numerous other health parameters. Despite the amount of substantiated benefits associated with school gardening education integration, few studies have systematically evaluated sustainability factors essential to the success of these programs.
Objective: The overall goal of this study is to evaluate the challenges and best practices predicting successful sustainability of school gardens in the Greater Austin area.
Methods: We assembled a panel of experts to develop surveys targeting administrators and teachers to assess fundamental barriers and strategies relevant to school gardening programs, as well as an observational evaluation tool of the physical garden landscape. We administered these 35-item surveys to 523 school teachers and 174 administrators and completed the observation logs from 100 schools across the Austin area. Descriptive and frequency analyses will be run to identify the top barriers reported and strategies implemented. Subsequently, schools will be categorized based on status of the physical gardens, teacher usage/integration of garden, and number of children using the garden, to categorize schools as thriving vs. struggling garden programs. Regression analysis will be run to assess which strategies/barriers predict thriving garden programs.
Conclusion: The results of this study will identify key components needed to maintain and sustain successful school gardening programs.Nutritional Science
Abstract 4104: Moderate calorie restriction activates autophagy during tumor growth suppression
No full text
